1921
image of Targeting IL-27 and/or IL-10 in Experimental Murine Visceral Leishmaniasis
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645
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Abstract

Interleukin-10 (IL-10) and interleukin-27 (IL-27) both exert counterregulatory immunodeactivation in visceral infection. We studied experimental infection in the livers of IL-10 and IL-27Rα mice and observed that in IL-27Rα, but not IL-10 mice, interferon-gamma (IFN-γ) and tumor necrosis factor (TNF) were required for heightened granulomatous inflammation and accelerated control of intracellular parasite replication. This difference in mechanism, along with residual IL-10 activity in IL-27Rα mice, suggested targeting IL-27 in addition to IL-10 in a macrophage-activating, anti-counterregulatory cytokine treatment strategy. In C57BL/6 wild-type mice with established liver infection, a single injection of anti–IL-27 p28 or anti–IL-10R monoclonal antibody enhanced granuloma assembly, enabled macrophage activation, and induced comparable parasite killing (49–56%). However, anti–IL-27 p28 plus anti–IL-10R combination treatment did not increase leishmanicidal effects. These results suggest that IL-27 and IL-10 may operate in a linked deactivating mechanism and that in this intracellular infection, either IL-27 or IL-10 is a suitable immunotherapeutic target.

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/content/journals/10.4269/ajtmh.20-0531
2020-08-17
2020-09-22
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http://instance.metastore.ingenta.com/content/journals/10.4269/ajtmh.20-0531
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  • Received : 22 May 2020
  • Accepted : 13 Jul 2020
  • Published online : 17 Aug 2020
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